Ligand field and polarity tuning of Fe(ii) complexes for selective ROS-mediated anticancer activity

Abstract

A redesigned N5-type ligand that strengthens the donating ability while reducing polarity was utilized to generate an Fe(ii) complex. This modification reorganized the metal-centered electronic structure, producing red-shifted pi-pi* and LMCT transitions and enabling oxidation at a substantially lower potential. The resulting complex exhibited enhanced hydroxyl radical generation and improved cellular uptake, leading to pronounced and selective ROS elevation in renal cancer cells with minimal effects on normal fibroblast cells. These results demonstrate that concurrent tuning of ligand-field strength and molecular polarity constitutes an effective strategy for developing redox-active iron complexes with selective anticancer activity.